Rotating Substrate Cell Sorter Using Centrifugal Force and Magnetic Fields
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Solution Overview
Problem
Current cell sorting technologies, such as FACS flow cytometers and magnetic bead-based systems, face challenges in preserving cell integrity and achieving high throughput, particularly in isolating rare cells like circulating tumor cells from whole blood samples, with many methods causing cell damage or being impractical for large-scale processing.
Innovation Solution
A cell sorting system utilizing a rotatable substrate that generates centrifugal force and dielectrophoresis electric fields to sort cells, featuring a bifurcation in microfluidic channels and adjustable electrode pins to immobilize target cells, allowing for high-throughput sorting without fluorescent labels and preserving cell integrity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If FACS flow cytometer is used for cell sorting, then cell sorting capability is achieved, but cell viability deteriorates and cell loss exceeds 50 percent
Solution Approach 1:
The patent replaces the mechanical shearing and hydrodynamic forces of FACS with a magnetic field-based sorting mechanism. Magnetic particles conjugated to target cells interact with a magnetic field to deflect cells into collection reservoirs, eliminating the high-velocity fluid dynamics that cause cell damage in FACS systems.
Solution Approach 2:
The patent introduces magnetic particles as an intermediary between the sorting mechanism and target cells. These magnetic beads conjugate with antibodies specific to target cell markers, providing a gentle means to manipulate and sort cells without direct mechanical stress on the cells themselves.
2Productivity
If magnetic particles are used to conjugate with target cells for sorting, then cell sorting is achieved, but cell behavior is altered downstream
Solution Approach 1:
The patent optimizes magnetic particle parameters including size (0.5-5 μm), concentration, and magnetic field strength to achieve effective sorting while minimizing impacts on cell behavior. The magnetic field gradient is carefully controlled to provide sufficient sorting force without excessive mechanical stress on cells.
3Reliability
If MACSQuant cell sorter with diaphragm is used, then cell integrity is preserved, but multiplexing configuration is not available
Solution Approach 1:
The patent divides the sorting system into multiple independent magnetic actuation zones, each capable of deflecting cells into different collection reservoirs. This segmented approach enables simultaneous sorting of multiple cell populations (multiplexing) while maintaining the gentle magnetic field-based mechanism that preserves cell integrity.
4Reliability
If DEPArray system with disposable chips is used, then dielectrophoresis sorting is achieved, but throughput is limited and processing cost is high
Solution Approach 1:
The patent employs magnetic particles that can be conjugated with various antibodies for different target cell markers, making the same hardware platform universally applicable to multiple sorting applications. This eliminates the need for expensive disposable chips with embedded electrodes for each sorting task, significantly reducing per-sample cost while maintaining sorting precision.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The system effectively sorts cells with high throughput and preserves cell integrity, enabling efficient isolation of rare cells like CTCs from whole blood samples, improving upon existing methods by reducing cell damage and increasing practicality for large-scale processing.
Implementation Method 1
The rotatable substrate is configured to rotate around a rotation axis to generate a centrifugal force
Implementation Method 2
an electrode operable to generate a dielectrophoresis electric field to immobilize the target cell
Data Source
AI summary
A device for sorting cells includes a rotatable substrate (601) configured to rotate around a rotation axis (611) to generate a centrifugal force and a cover layer (441) attached to the rotatable substrate (601). The rotatable substrate (601) includes a sample reservoir (602) disposed at the center of the rotatable substrate (601), a flow path (604) coupled to the sample reservoir (602) and extending radially towards a periphery of the rotatable substrate (601) and including a bifurcation (606) into a main channel (607) and a side channel (608). The rotatable substrate (601) moves a plurality of cells stored in the sample reservoir (602) to a periphery of the rotatable substrate (601) by a centrifugal force. The cover layer (441) includes a first opening in fluid communication with the main channel (607) and a second opening in fluid communication with the side channel (608).